rs17199888

Variant names:

• chr7-34824727-G-A
• rs17199888
• NM_207172.2:c.479-2674G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207172.2(NPSR1):​c.479-2674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,962 control chromosomes in the GnomAD database, including 2,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2719 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 3 publications found

Genes affected

NPSR1 (HGNC:23631): (neuropeptide S receptor 1) This gene encodes a member of the vasopressin/oxytocin subfamily of G protein-coupled receptors. The encoded membrane protein acts as a receptor for neuropeptide S and affects a variety of cellular processes through its signaling. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Polymorphisms in this gene have also been associated with asthma susceptibility, panic disorders, inflammatory bowel disease, and rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPSR1-AS1 (HGNC:22128): (NPSR1 antisense RNA 1) This gene is located within a region that has been associated with asthma susceptibility. The locus is considered non-protein-coding based on lack of protein homology and a lack of experimental support for an encoded protein. Three alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207172.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.479-2674G>A		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.479-2674G>A		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.479-2674G>A		intron	N/A	NP_997056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.479-2674G>A		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.479-2674G>A		intron	N/A	ENSP00000370950.3
	NPSR1	ENST00000359791.5	TSL:1	c.479-2674G>A		intron	N/A	ENSP00000352839.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27783 AN: 151842 Hom.: 2711 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27818 AN: 151962 Hom.: 2719 Cov.: 32 AF XY: 0.184 AC XY: 13671 AN XY: 74262

African (AFR) AF: 0.164 AC: 6783 AN: 41458

American (AMR) AF: 0.157 AC: 2395 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1614 AN: 5126

South Asian (SAS) AF: 0.0999 AC: 481 AN: 4816

European-Finnish (FIN) AF: 0.271 AC: 2857 AN: 10540

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12721 AN: 67948

Other (OTH) AF: 0.175 AC: 370 AN: 2116

Alfa AF: 0.185 Hom.: 1412

Bravo AF: 0.178

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.79
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17199888; hg19: chr7-34864339;